a multiple dose study of grazoprevir (mk-5172) in hepatitis c-infected participants (mk-5172-010)

Conditions: Hepatitis C

Summary: the goal of this study was to compare hepatic pharmacokinetics (pk) derived from liver tissue to plasma pk after administration of grazoprevir (mk-5172) to participants with chronic hepatitis c virus (hcv) infection. participants will be randomized to one of four different liver ultrasound-guided fine needle aspirate (fna) schedules (at 4-, 8-, 24-, or 72-hours after the day 7 dose).


Eligibility criteria:
inclusion criteria: * has a body mass index (bmi) ≥18.5 kg/m² and ≤36.0 kg/m² * has chronic compensated, genotype 1 hcv infection * has no cirrhosis of the liver as confirmed by fibrosure®/fibro test® and/or local country procedure (e.g. transient elastography/fibroscan) * does not require anticoagulants, nonsteroidal anti-inflammatory agents, and aspirin for at least fourteen (14) days preceding the initial liver biopsy and continuing throughout the entire study * if is a female participant of reproductive potential, is willing to use 2 medically acceptable forms of contraception for 2 weeks prior to start of treatment through 2 weeks after last study treatment * if is a male participant with a partner(s) of reproductive potential, is willing to use 2 medically acceptable forms of contraception from first dose to 90 days after last dose exclusion criteria: * has a history of stroke, chronic seizures, or major neurological disorder * has received previous treatment with a direct-acting antiviral (daa) * has evidence of high grade bridging fibrosis from prior liver biopsy within 3 years of study entry * has evidence or history of chronic hepatitis not caused by hcv infection including but not limited to non-hcv viral hepatitis, nonalcoholic steatohepatitis (nash), drug-induced hepatitis, or autoimmune hepatitis * has clinical or laboratory evidence of cirrhosis or other advanced liver disease * has decompensated liver disease as indicated by a history of ascites, hepatic encephalopathy, or bleeding esophageal varices * has been diagnosed with, or suspected of having, hepatocellular carcinoma (hcc) * has clinically significant abnormality on an electrocardiogram (ecg) * is co-infected with human immunodeficiency virus (hiv) * is positive for hepatitis b surface antigen (hbsag) or other evidence of active hepatitis b infection * has a history of gastric bypass surgery, bowel resection or other disorder that may interfere with absorption * has a history of clinically significant uncontrolled endocrine, gastrointestinal, cardiovascular, hematological, immunological, renal, respiratory, or genitourinary abnormalities or diseases * has clinically significant neoplastic disease * uses alcohol to excess, defined as greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer \[354 ml\], wine \[118 ml\], or distilled spirits \[29.5 ml\]) per day * is a current regular user (including use of any illicit drugs) or history of drug (including alcohol) abuse within the last 3 months * has undergone surgery, donation of 1 unit of blood (approximately 500 ml) or participation in another investigational study within a period of 4 weeks prior to the screening visit * has a history of multiple and/or severe allergies, or anaphylactic reaction or intolerability to prescription or nonprescription drugs or food * is pregnant or lactating * is expecting to donate eggs or sperm